The synthesis of inorganic metal colloidal particles, e.g., colloidal particles of Ag, Au, and Co, has been described in numerous publications. Proteins can be absorbed quite strongly onto the surface of these metal colloids. The protein-metal particles possess many biological applications, including cell labeling, cell separation and diagnostics, Cais, M. et al., Nature 270:534 (1974); Poynton, C. H. et al., Lancet 1:524 (Mar. 5, 1983).
The synthesis of polymeric microspheres containing metals has been disclosed in several patents, e.g. Yen et al., U.S. Pat. No. 4,157,323, issued June 5, 1979 at Col. 2, lines 37-56 and Col. 6, lines 22-38; Rembaum et al., U.S. Pat. No. 4,267,235, issued May 12, 1981 at Col. 2, lines 42-46, Col. 3, lines 32-34 and Col. 3, line 51-Col. 4, lines 10; and Rembaum, U.S. Pat. No. 4,413,070, issued Nov. 1, 1983, at Col. 3, line 65-Col. 4, line 1 and Col. 6, line 12-41, as well as in West German Application No. P3224484.3, filed June 30, 1982 in the name of Yeda Research and Development Co., Ltd., and published Jan. 20, 1983. These metal-containing microspheres were obtained by entrapping the metal during the polymerization process. Polymeric microspheres so produced and which contain iron particles were used primarily for cell separation via a magnetic field. The synthesis of polyamino microspheres containing various metals, e.g. metal-containing polyvinyl pyridine copolymeric microspheres, is disclosed in Rembaum et al., U.S. Pat. No. 4,197,220, issued Apr. 8, 1980 at Col. 3, lines 3-20, 41-50 and Col. 5, line 31, Col. 6, line 10.
Various types of polyaldehyde microspheres and their syntheses are known, e.g. polyglutaraldehyde microspheres, Rembaum et al., U.S. Pat. No. 4,267,235; polyacrolein microspheres, W. German Application No. P 3224484.3 (via base catalysis, redox initiation or irradiation initiation) and Rembaum, U.S. Pat. No. 4,413,070 (irradiation initiation) and agarose encapsulated polyaldehyde microsphere beads, European Application No. 83 101 88 3.3, filed Feb. 25, 1983 in the name of Yeda Research and Development Co., Ltd., and published Sept. 7, 1983. Polyacrolein microspheres and agarose-polyacrolein microsphere beads are additionally disclosed in several papers including Margel, Beitler and Offarim, Immunological Commun. 10 (7): 567-575 (1981); Margel, Ind. Eng. Prod. Res. Dev. 21: 343-348 (1982); Margel, Beitler and Offarim, J. Cell Science 56: 157-175 (1982); Marcus, Offarim and Margel, Biomat., Med. Dev., Art. Org. 10(3): 157-171 (1982); Margel, FEBS Letters 145(2):341-344 (1982) and Margel and Offarim, Analyt. Biochem. 128: 342-350 (1983).
Of the above-mentioned patents and patent applications U.S. Pat. No. 4,413,070 at Col. 3, lines 62-64 and Col. 8, lines 27-32 and European Application No. 83 101 88 3.3, P. 12, example 22 also disclose the use of various microspheres to chelate salts or other metal-containing compounds. See also Margel, FEBS Letters 145(2):341-344 (1982); Margel and Hirsh, Biomat., Med. Dev., Art. Org. 9(2):109-125 (1982); and Margel, J. Med. Chem. 24(10):1263-1266(1981).
Heretofore, however, polymeric microspheres containing elemental metals and aldehyde groups available for convenient derivatization of the microspheres with amino ligands have not been disclosed.
It is therefore an object of the present invention to provide such metal-containing polyaldehyde microsphere. It is an additional object of this invention to provide methods for preparing such microspheres. It is a further object of this invention to provide methods for using such microspheres in various applications.